Hearts exposed to sustained hemodynamic overload undergo molecular, cellular, muscular, and chamber morphologic changes that are typically maladaptive and contribute to progressive cardiac dysfunction and ultimately heart failure. Pathophysiological stimuli that trigger such responses include hypertension, valvular disease, neurohormonal stress, and excessive chamber filling associated with a decline in pump function. These trigger alterations in multiple cellar signaling and transcription pathways that induce muscle cell growth, worsened function of the heart muscle, hypertrophic remodeling and cardiac dilation. Existing therapies cannot adequately prevent these pathological changes. Enlargement of the heart is a chronic and progressive condition that ultimately results in heart failure. Heart failure affects over 5 million Americans, with more than 500,000 new diagnoses annually in the United States alone, and remains the leading cause of death. Nearly half of these patients have hypertension and cardiac hypertrophy with apparent preservation of contraction of the heart, a syndrome for which there are currently no specifically tested and approved treatments. Improved therapeutic compositions and methods for the treatment of cardiac conditions, such as cardiac hypertrophy, are urgently required.